Project Summary Age-dependent olfactory decline (presbyosmia) is widely present in many species, including humans. At least fifteen million Americans over 55 years old suffer from presbyosmia. By affecting the well-being, quality of life, and overall health, presbyosmia presents a significant challenge to public health. Patients with presbyosmia often show a decreased interest in food, can withdraw socially, and exhibit higher rates of depression. Furthermore, many age-related neurological diseases, including Parkinson's disease and Alzheimer's disease, are commonly associated with olfactory dysfunction. In fact, olfactory loss often precedes various motoric symptoms in these deadly neurological diseases. Despite the importance of olfaction to human physiology and health, the cellular and molecular mechanisms underlying presbyosmia are poorly understood (knowledge gap). As a major cell type in the nervous system, glial cells are typically considered as passive modulators during neural development and synaptic transmission. Whether glial cells play active roles in sensory transduction and brain aging is not well understood. C. elegans is a well-established model organism for neuroscience and aging research due to its simple nervous system, short lifespan, and powerful genetic tools. Very importantly, genetic studies from multiple model organisms have shown that the evolutionarily conserved genetic programs and signaling pathways play pivotal roles in regulating sensory transduction and aging process across species. This proposal will bring together in vivo calcium imaging, optogenetics, molecular genetics, and behavioral analysis to investigate and discover the molecular mechanisms through which the olfactory glial cells play active roles in odorant detection and age-dependent olfactory decline. Since both olfaction and aging are regulated by the evolutionarily conserved genes and signaling pathways, our innovative studies on C. elegans glial cells in olfaction and age-associated olfactory decline will provide mechanistic insights into similar processes in other species.